[HN Gopher] Scientists Discover a Cause of Lupus, Possible Way t...
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Scientists Discover a Cause of Lupus, Possible Way to Reverse It
Author : adamredwoods
Score : 94 points
Date : 2024-07-10 21:24 UTC (1 hours ago)
(HTM) web link (news.feinberg.northwestern.edu)
(TXT) w3m dump (news.feinberg.northwestern.edu)
| ipunchghosts wrote:
| I wonder if any of these findings help us better understand
| me/cfs.
| galangalalgol wrote:
| It has been my hope that the number of me/cfs cases would
| finally drive enough research into autoimmune disorders in
| general, that we might finally figure it out. It seems very
| poorly understood from an outside perspective.
| PaulKeeble wrote:
| There is no funding and since Long Covid appeared the funding
| for ME/CFS has completely vanished. If Long Covid ME like
| illness is the same then ME/CFS is getting lots of research
| right now, on the other hand if they turn out to be different
| ME/CFS patients are getting completely ignored.
| thenerdhead wrote:
| Many ME experts are doing both. RECOVER is considering
| adding ME/CFS arms to its huge clinical trial platform.
| UCSF just added ME/CFS as a priority in their LIINC
| program.
|
| SARS-CoV-2 therapeutics won't work on both but immune cell
| based ones may given they haven't been tested in either
| yet.
|
| Both suggest a root cause of persistent viral antigen. Time
| will tell what works here.
| PaulKeeble wrote:
| Maybe but the immune dysfunction goes further in ME/CFS its not
| just a problem of reduced CD4 and heightened CD8 (which are the
| two cell types they seem to be talking about) its a wider set
| of oddities that seem related to exhausted cells with not
| enough energy stuck in "there is infection near by" operation
| mode. It might help reduce symptoms that are caused by the
| imbalance so it would certainly be worth a trial when they work
| out the details.
| BenFranklin100 wrote:
| Autoimmune diseases, of which lupus is but one of many, are
| essentially black boxes. It's proven extraordinarily difficult to
| develop therapies in this area. As such, this is great news.
| Hopefully this research will encourage pharmaceutical and biotech
| companies to invest more resources into translating research
| findings into effective therapies.
|
| I haven't read the paper yet, so I can't comment on how this
| discovery might generalize to other autoimmune diseases, but one
| interesting bit about autoimmune diseases is that they tend to
| run in packs. This is suggestive there may be underlying
| mechanisms that are shared across autoimmune diseases.
| atombender wrote:
| The aryl hydrocarbon receptor (AhR), which is key to this
| discovery, appears to be super relevant to psoriasis, another
| autoimmune disease.
|
| AhR has been known for a long time, but it seems it's been
| somewhat mysterious until a series of recent breakthroughs. In
| 2022, an AhR inhibitor called tapinarof, sold as VTAMA, was
| launched, and has shown itself to be one of the most effective
| treatments for psoriasis to date. It's also unique in that it
| appears to have the ability to bring lasting remission. In the
| main clinical trial, patients who used VTAMA for one year and
| then stopped had a mean remission duration of 4 months until
| their psoriasis returned. That is unheard of for any topical
| medication used on psoriasis.
|
| Blocking AhR has also shown promise in treating MS [1].
|
| I haven't read the lupus paper, but often with papers like
| these, the "cause" turns out not to be the actual origin, but
| some cytokine or other protein that is more disease-specific
| than current drug targets. This lupus discovery appears to
| identify an imbalance that may be compensated for, but we still
| don't know what triggers the imbalance in the first place.
|
| In some cases diseases turn out to be a genetic fault, but my
| money is on pathogens acting as the initial triggering event,
| which then spins the immune system into a vicious cycle of
| autoimmunity. In psoriasis we see this with strep bacteria, for
| example, but the exact mechanisms are not well understood.
| However, the mechanism that makes psoriasis chronic _has_ been
| identified, a type of T-cell called a tissue-resident memory
| (TRM) T-cell. This type of cell acts as a kind of biological
| memory for infections.
|
| [1] https://newsroom.uvahealth.com/2023/02/15/multiple-
| sclerosis...
| BenFranklin100 wrote:
| Great comment, thanks. I'm looking forward to reading the
| paper.
| kylehotchkiss wrote:
| I have a good feeling we're going to make a fairly big impact
| on cancer in our lifetimes with mRNA and other new discoveries
| in our lifetime. Autoimmune issues I'm feeling much less
| confident about. It seems like so many of the therapies are
| "turn down the immune system". I wish there was wider study
| into autoimmune derived mental health complications too. Maybe
| I'm totally wrong on this (and I'm very OK to be proven wrong)
| but maybe there's something to find here.
| trhway wrote:
| On one side we have in this article :
|
| " insufficient activation of a pathway controlled by the aryl
| hydrocarbon receptor (AHR), which regulates cells' response to
| environmental pollutants, bacteria or metabolites. Insufficient
| activation of AHR results in too many disease-promoting immune
| cells, called the T peripheral helper cells, that promote the
| production of disease-causing autoantibodies.
|
| To show this discovery can be leveraged for treatments, the
| investigators returned the aryl hydrocarbon receptor-activating
| molecules to blood samples from lupus patients. This seemed to
| reprogram these lupus-causing cells into a cell called a Th22
| cell that may promote wound healing from the damage caused by
| this autoimmune disease.
|
| "We found that if we either activate the AHR pathway with small
| molecule activators or limit the pathologically excessive
| interferon in the blood, we can reduce the number of these
| disease-causing cells,"
|
| On the other side quick search on AHR activation brings for
| example cancer related stuff like this :
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570930/
|
| "AHR activation to promote tumor cell intrinsic malignant
| properties and to suppress anti-tumor immune responses [14],
| [17], [18]. Specifically, the AHR drives cancer cell migration,
| invasion, and survival, regulates cell cycle progression and
| promotes cancer stem cell characteristics [14], [19], [20], [21],
| [22]. Simultaneously, it inhibits anti-tumor immunity "
|
| Human body by its complexity and our lack of understanding of it
| sometimes reminds the codebases i've worked on :)
|
| In that rabbit hole of articles on AHR there is also :
|
| https://www.nature.com/articles/s41423-020-00585-5
|
| "The aryl hydrocarbon receptor and the gut-brain axis"
|
| which in particular discusses what looks to me (i'm not a doctor)
| like a connection/correlation : gut microbes -> AHR ->
| glioblastoma.
| elcritch wrote:
| Both reactions make sense to me. Too much AHR activation
| suppresses immune response leading to cancer proliferation due
| immune cells not culling cancerous cells, but too little leads
| to auto-immune conditions. It's definitely like a large sloppy
| code base with lots of implicit overlaps and global effects.
| beekaywhopper wrote:
| script writers for House are shaking in their boots
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